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AN INVESTIGATION OF INDICATORS OF SOME CYTOKINES IN PATIENTS WITH CUTANEOUS LEISHMANIASIS IN THE PROCESS..,
Raximov Ilxom Raximovich, Ph D., SO "Republican Specialized Scientific Practical Medical Center of Dermatovenerology and Cosmetology" of the Ministry of Health of the Republic of Uzbekistan Tashkent city, Uzbekistan E-mail: i.rakhimov.75@bk.ru
AN INVESTIGATION OF INDICATORS OF SOME CYTOKINES IN PATIENTS WITH CUTANEOUS LEISHMANIASIS IN THE PROCESS OF TREATMENT
Abstract
The study of aspects of pathogenesis, diagnosis and treatment of cutaneous leishmaniasis is a very urgent problem in Uzbekistan, as the region is an endemic zone of the disease.
Background: The study of the state of the level of some signal molecules - cytokines and their dynamics as a result of pathogenetic treatment in patients with cutaneous leishmaniasis with the use of domestic medicinal product "Mexidol".
Methods: Clinical examination was carried out in 112 patients with cutaneous leishmaniasis who received inpatient treatment at the "Republican Specialized Scientific Practical Medical Center of Dermatovenerology and Cosmetology" of the Republic of Uzbekistan. The levels of cytokines IL-4, IL-6, IL-8, TNF-a were determined by the method of enzyme-linked immunosorbent assay (ELISA). Statistical analysis was carried out using Student's t-test.
Results: The results of the research showed that, with cutaneous leishmaniasis, there is an imbalance in cytokine indices, which depends on the clinical form and severity of the disease. The obtained data after the end of the traditional method of treatment in blood serum in patients with ulcerated leishmaniasis showed a tendency to decrease the content of proinflammatory cytokines - IL-6, IL-8 and TNF-a and a tendency to increase anti-inflammatory cytokine - IL-4 in comparison with data before treatment (p > 0.05). Comparative analysis of traditional and complex methods of treatment of cutaneous leishmaniasis revealed significant changes in favor of the use of complex treatment with Mexidol.
Conclusion: Thus, the developed complex method of treatment ofpatients with cutaneous leishmaniasis with the use ofMexidol and the external agent Fargals showed high therapeutic effectiveness in comparison with the traditional method of treatment. Since, this method of treatment contributed to the positive dynamics of clinical picture of the disease and restoration of detected violations of cytokine indices. This method of treatment can be recommended for further practical use as one of the pathogenetically grounded methods of treatment of cutaneous leishmaniasis.
Keywords: cutaneous leishmaniasis, cytokines, immunomodulators.
Introduction
In Uzbekistan, cutaneous leishmaniasis is one of the most common parasitic diseases that have a large specific gravity in the regional pathology. Quite high prevalence of zoonotic cutaneous leishmaniasis is noted in Turkmenistan and Uzbekistan, where tens and hundreds of new cases of the disease are registered annually in endemic areas [1; 2; 3].
Recently, an interest in synthesis, secretion of cytokine molecules, their receptors, natural antagonists has grown significantly and is of great importance due to the possibility of their use for the purpose of determining etiopathogenesis, diagnosis, monitoring of the effectiveness of treatment [7].
Despite a wide range of preventive measures that serve to reduce morbidity, it is not always possible to ensure its
complete elimination, and therefore the problem of treating patients with cutaneous leishmaniasis remains one of the most important problems in dermatology today [4; 5; 6; 9].
In this regard, the search for new effective drugs, for treatment of patients with cutaneous leishmaniasis is a very urgent issue [8; 10; 11; 12].
Methods
The influence of the developed method of treatment and traditional therapy on the indices of some cytokines (IL-4, IL-6, IL-8, TNF-a) was studied in 112 patients with cutaneous leishmaniasis. 38 patients with tuberculous cutaneous leishmaniasis (14 patients received traditional and 24 complex therapies), 52 with ulcerated leishmanias (21 patients received traditional and 31 complex therapy) and 22 patients with ulcerated leishmanias
with tubercles of seeding with lymphangitis (6 patients received traditional and 16 - complex therapy).
Cytokines in the blood serum were determined by the method of enzyme immunoassay (EIA). The test systems developed at the State Scientific Research Institute of Highly Pure Biopreparations (SPb) were used for determining the cytokines.
The results of the research were statistically processed using standard methods of variational statistics using the Student's t-test using the Excel-0ffice-2010 application program on a Pentium IV computer.
Results and discussion
Our previously conducted studies have shown that with cutaneous leishmaniasis in the serum of blood, certain violations of cytokine indices are detected. The revealed violations of cytokine indices depend on the clinical forms of the disease. In mild forms (tubercle form and ulcerated leishmanioma), the content of cytokines studied varies less, and in severe forms (ulcerated leishmanias with tubercles of seeding with lymphangitis) cutaneous leishmaniasis is greater.
Taking into account the abovementioned, we used the "Mexidol" drug to restore the detected disorders in cytokine indices in the complex of therapy for patients with cutaneous leishmaniasis and locally used the "FarGals" drug for accelerating the healing of wounds.
Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate)
after N. M. Emanuel, the Scientific Research Institute of Pharmacology of the Russian Academy of Medical Sciences and the All-Union Scientific Center for the Safety of Biologically Active Substances. Mexidol is an inhibitor of free radical processes, a membrane protector. The drug improves microcirculation and rheological properties of blood, reduces platelet aggregation, which has an antitoxic effect and increases the regenerative potential of tissues.
FarGals was developed for the first time in Uzbekistan, the composition of the drug is aqueous extract from the medium of cultivation of autotrophic iron-oxidizing bacteria. It has a pronounced antimicrobial effect and reliable wound healing activity.
Meksidol was used intramuscularly at 100 mg twice a day for 14 days.
FarGals: locally in the form of applications, in dilution with distilled water in a ratio of1:1, 2 times a day for 20 days.
The results of the study showed (Table 1) that in the serum of patients with tubercle cutaneous leishmaniasis after the end of treatment with a traditional method, there is a tendency to decrease the concentration of IL-6, IL-8 and TNF-a (p > 0.05) to an increase in IL-4 (p > 0.05) compared to pre-treatment data. This indicates that traditional therapy does not have the expected positive effect in restoring the observed disorders in the cytokine indices of patients with tubercle cutaneous leishmaniasis.
was developed by the Institute of Biochemical Physics named
Table 1. Comparative analysis of the effect of therapy conducted on cytokine indices in patients with tubercle cutaneous leishmaniasis (M±m)
Cytokine status indicators Method of therapy
Traditional therapy n = 14 Complex therapy n = 24
IL-4 (pg/ml) 1.67 ± 0.16 1.67 ± 0.12
1.88 ± 0.15 2.02 ± 0.11**
IL-6 (pg/ml) 190.50 ± 3.90 190.44 ± 3.59
180.63 ± 3.83 173.27 ± 3.46*
IL-8 (pg/ml) 92.73 ± 2.25 92.03 ± 2.65
84.70 ± 2.19 77.09 ± 2.64*
TNF-a (pg/ml) 32.17 ± 2.72 30.14 ± 1.84
28.04 ± 2.43 21.72 ± 1.45**
Note: in the numerator - data before treatment; in denominators - data after treatment p - reliability of data with respect to indicators before treatm *- p < 0.05; **- p < 0.01
When studying the effect of complex therapy on cytokine indices in patients with tubercle cutaneous leishmaniasis, it was revealed that after the treatment with this method, the content of IL-6 (p < 0.05), IL-8 (p < 0.05) and TNF-a (p<0.01), the onset significantly decreased compared to pre-treatment data. Along with this, in patients of this group after
treatment, the concentration of IL-4 significantly increased (p < 0.01) in relation to the data before treatment (Table 1). It should be noted that after the treatment with this method, the IL-4 index reached the control value.
In patients with ulcerated leishmanias after the traditional method of treatment in the serum, there is a tendency to de-
AN INVESTIGATION OF INDICATORS OF SOME CYTOKINES IN PATIENTS WITH CUTANEOUS LEISHMANIASIS IN THE PROCESS...
crease the content of IL-6, IL-8 and TNF-a (p > 0.05) and to increase IL-4 (p > 0.05) in comparison with the data before the treatment. This indicates that the traditional method of therapy also fails to achieve the expected positive result in restoring the imbalance in the cytokine indices of patients with ulcerated leishmanias (Table 2).
A study of the effect of the complex treatment on cyto-kine indices in patients with ulcerated leishmanias showed
Table 2. - Comparative analysis of the cytokine indicators in patients with
that after the treatment with this method in serum, the concentration of cytokines IL-6, IL-8 and TNF-a significantly decreased with respect to the data before treatment (p < 0.05). In patients of this group after treatment, the level of IL-4 significantly increased (p < 0.01) compared to the data before treatment (Table 2). However, they did not reach the indicators of control value.
effect of the conducted therapy on ulcerated leishmanias (M ± m)
Cytokine status indicators Method of therapy
Traditional therapy n = 21 Complex therapy n = 31
IL-4 (pg/ml) 1.48 ± 0.09 1.58 ± 0.11
1.62 ± 0.07 1.82 ± 0.09**
IL-6 (pg/ml) 183.87 ± 3.55 183.55 ± 3.01
177.72 ± 3.34 172.85 ± 2.74*
IL-8 (pg/ml) 88.58 ± 2.77 83.63 ± 2.55
83.15 ± 2.80 74.84 ± 2.42*
TNF-a (pg/ml) 30.61 ± 2.05 26.45 ± 1.91
26.96 ± 1.83 22.39 ± 1.53*
Note: in the numerator - data before treatment; in denominators - data after treatment p - reliability of data with respect to indicators before treatment *-p < 0.05; **-p < 0.01
A similar situation was revealed when studying the effect tients with ulcerated leishmaniomas with tubercles of seeding of applied methods of therapy on cytokine indicators in pa- with lymphangitis.
Table 3. - Comparative analysis of influence of the conducted therapy on cytokine indices in patients with ulcerated leishmaniomas with tubercles of seeding with lymphangoites (M ± m)
Cytokine status indicators Method of therapy
Traditional therapy n=6 Complex therapy n=16
IL-4 (pg/ml) 1.43 ± 0.22 1.49 ± 0.14
1.61 ± 0.20 1.82 ± 0.13*
IL-6 (pg/ml) 196.32 ± 6.33 203.72 ± 5.12
191.20 ± 6.25 186.54 ± 6.60
IL-8 (pg/ml) 94.14 ± 3.20 99.62 ± 4.43
88.85 ± 2.88 87.55 ± 3.95
TNF-a (pg/ml) 41.56 ± 3.04 38.64 ± 3.31
37.67 ± 2.84 31.68 ± 3.04
Note: in the numerator - data before treatment; in denominators - data after treatment p - reliability of data with respect to indicators before treatment *- p < 0.05;
The obtained data showed (Table 3) that in the serum of blood in patients with ulcerated leishmaniomas with tubercles of seeding with lymphangites after the traditional method of treatment, there is also a tendency to decrease the content of IL-6, IL-8 and TNF-a and a tendency to increase IL-4 compared with the data before treatment (p > 0.05).
When studying the effect of complex treatment on cy-tokine values in patients with ulcerated leishmaniomas with tubercles of seeding with lymphangitis, it was revealed that after treatment with this method in serum, the concentration of cytokines IL-6, IL-8 and TNF-a decreased compared to indicators before treatment, however they were statistically
unreliable (p > 0.05). Along with this, in patients of this group after treatment, the concentration of IL-4 significantly increased (p<0.05) with respect to the data before treatment. However, they did not reach the values of the control group (Table 3).
Conclusion
Thus, the complex method of treatment for patients with cutaneous leishmaniasis developed by us helps to restore the
detected violations of cytokine indices. However, this method of treatment has a more effect only in patients with tubercle cutaneous leishmaniasis, and in patients with ulcerated leish-maniomas and ulcerated leishmanias with tubercles of seeding with lymphangites, complete recovery of the detected cytokine indices is not achieved. In this regard, it is advisable to conduct a repeat course of therapy in patients with these clinical forms of cutaneous leishmaniasis.
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